How can I correct PK model if I get large RSE on parameter estimates

1 messages 1 people Latest: Jan 25, 2016
Dear Dr.Ayyappa Thanks for suggestion. You were right. I checked the model without RUV and found that model run successfully without any error message. Minimization was successful with OFV value of 501.08 (OFV of previous run 477.71). Also I observed that there was no significant difference in the parameter estimates and basic GOF plots from previous model (both additive and proportional RUV) and current model (proportional RUV only). I think now it is crystal clear that additive RUV was not required. thankyou Best Regards, Swati Swati Jaiswal PhD Scholar (CSIR-Senior Research Fellow) Pharmacokinetics & Metabolism Division CSIR-Central Drug Research Institute *Lucknow-226031, India* *Mobile +91 9473837970*
Quoted reply history
On Fri, Jan 22, 2016 at 3:06 AM, Ayyappa Chaturvedula <ayyappach_at_gmail.com> wrote: > Swati, > > Did you run a model without additive RUV and checked if it is required? > > Best Regards, > Ayyappa > > On Jan 21, 2016, at 2:44 AM, swati j <swatijaiswal.bhu_at_gmail.com> wrote: > > Dear members of nmusers: > > I am trying to do PopPK analysis of plasma concentration-time data obtained from a non-steady-state PK study of a drug in hamsters (at 2 doses; 10 mg/kg and 20 mg/kg, p.o for 5 consecutive days at interval of 24 hr). > > after executing the model file(one compartment model with first order absorption), the result indicated successful minimization, but with one WARNING messgae : > > "*Large relative standard errors found, * > > *additive RUV 0.363451"* > > Please suggest What should I do next?....How I can reduce the RSE and what should be my next step to improve the model > > the model file which i used is as follows > > $PROBLEM PK model 1cmt > > $INPUT ID TIME DV AMT ADDL II MDV > $DATA paginPK4.csv IGNORE=# > $SUBROUTINE ADVAN2 TRANS2 > $PK > KA=THETA(1)*EXP(ETA(1)) > CL=THETA(2)*EXP(ETA(2)) > V =THETA(3) > SC=V/1000 > STRT = 0 > $THETA (0,0.338111) ; KA > (0,11.4608) ; CL total > (0,1049.2) ; V2 > $OMEGA 0.0423895 ; KA > 0.0143127 ; cl > $SIGMA 0.0640523 ; proportional RUV > 0.00105349 ; additive RUV > $ERROR > IPRED = F > IRES = DV-IPRED > W = DV > IWRES = IRES/W > Y = IPRED*(1+EPS(1)) + EPS(2) > > $ESTIMATION METHOD=1 INTERACTION MAXEVAL=9999 SIG=3 PRINT=5 NOABORT > POSTHOC > $COVARIANCE PRINT=E > ;$SIM (1234) NSUBPROBLEMS=1 ONLYSIM > $TABLE ID TIME DV PRED IPRED RES WRES IRES IWRES CL V KA AMT DV > NOAPPEND NOPRINT ONEHEADER FILE=out8.tab ; Xpose > $TABLE ID TIME DV IPRED IRES IWRES CWRES NOPRINT ONEHEADER > FILE=sdtab8 > $TABLE ID KA CL V NOPRINT ONEHEADER FILE=patab8 > $TABLE ID NOPRINT ONEHEADER FILE=cotab8 > $TABLE ID NOPRINT ONEHEADER FILE=catab8 > > thanks in advance > > > Regards > > Swati > > Swati Jaiswal > > PhD Scholar (CSIR-Senior Research Fellow) > > Pharmacokinetics & Metabolism Division > > CSIR-Central Drug Research Institute > > *Lucknow-226031, India* > > *Mobile +91 9473837970 <%2B91%209473837970>* > >